Higher TNM Stage Research Articles

Establishment of a nomogram predictive model for survival and prognosis of 97 patients with different subtypes of lung adenocarcinoma after radical resection.

e20596 Background: Postoperative recurrence and metastasis of lung adenocarcinoma (LUAD) is a major obstacle to long-term survival, and how to identify patients at high risk of recurrence / death after surgery and those likely to benefit from adjuvant therapy is currently a clinically relevant question. In this study, we investigated the survival characteristics of patients with different subtypes of LUAD after radical resection and established predictive prognostic models to inform postoperative management, recurrence prediction and risk management in lung cancer patients. Methods: A retrospective analysis of 97 patients who underwent concurrent genetic testing for LUAD radical resection at The Affiliated Tumor Hospital of Xinjiang Medical University between December 01, 2014 and December 30, 2017 was performed. A COX proportional risk regression model was used to construct a prognosis model for patients with LUAD after surgery and visualization of the model was performed using column diagrams. The performance of the model was evaluated using C index, calibration curve, and ROC curve. Results: (1)46 patients (47.42%) were included and 51 patients died (52.58%), with a median survival of 78 months (95% CI: 63-93). Twenty of these patients had a good prognosis (20.62%) and 77 had a poor prognosis (79.38%), with a median survival time of 88 months (95% CI: 81-95). The overall survival rate was 98.9%, 78.3% and 59.7%, respectively, and the cumulative disease-free survival rate was 77.3%, 37.1% and 20.6%, respectively, for 1, 3 and 5 years. Pathologic types were lepidic, acina/papillaryand solid/micropapillary with 87.50%, 56.90% and 58.80% OS and DFS, respectively. 37.50%、80%、11.80%. (2)26 patients (26.8%)had recurrent metastasis,the main site of metastasis was extrapulmonary, and multiple metastases were more common. (3)Univariateand multivariate analysis showed that TNM stage III, pathological classification as solid/micropapillary, tumor diameter ≥ 3cm, and gene mutation positivity were independent risk factors for prognosis in patients with lung adenocarcinoma after surgery. Based on the above risk factors, the Nomogram prognostic model was established with a C index of 0.687 (95% CI: 0.622-0.752) and calibration curves and ROCs for the 1, 3, and 5 year models, respectively, with AUC values of 0.742, 0.752, and 0.820 > 0.7, suggesting that the model is within the acceptable range of partitioning and accuracy, with the highest AUC for the 5-year DFS prediction. Conclusions: High TNM staging, pathotyping of micronipples or entities, ≥ 3cm tumor diameter, and mutant positivity were independent risk factors for recurrence and metastasis in patients with LUAD. The Nomogram predictive model based on patient risk factors after LUAD radical resection is effective in predicting long-term survival and guiding personalized treatment.

Blood Group Characteristics in Rectal Cancer. A study Conducted in a Tertiary Care Center, Srinagar, Kashmir, India

Introduction: Rectal cancer is the third most common cancer in the world. Tumors are most commonly located in the rectosigmoid region. There are many actors in the etiology such as age, geographical features, family history, obesity, diet, and history of malignancy. Blood groups are one of the controversial etiologic factors in CRC. Blood group antigens, covered by Karl Landsteiner in 1901, have been the subject of numerous cancer studies since 1953, when Aird declared that blood group A was associated with stomach cancer. Aim: In the present study, we aimed to determine the effect of blood group characteristics, which play a role in the etiology of Rectal cancer. Method: We Prospectively reviewed the patients who were diagnosed with CRC and operated in our center or at other centers and were followed postoperatively at our centers. Age, gender, histologic TNM stage (tumor, lymph node involvement, and metastasis), tumor-bearing colonRectal segment, ABO blood group, and Rh antigen were examined from the patients’ records. Results: Total of 60 patients with histopathologically confirmed as rectal cancers formed the study population. The male to female ratio in rectal cancers was 1.7:1. The age group varied from 16 to 80 years with most common age group in rectum cancer were between age is 45-64 years constituted (29) 48%. However, we observed relationship in the present study between Rh antigen and lymph node metastasis, liver metastasis, or TNM stage. O Blood group and rh positive was associated with lymph node involvement, higher TNM stage, and also found that risk of liver metastasis. Conclusion: As in Rectal cancer, our findings show that the O (+) blood group is a risk factor in rectal cancers, which have multifactorial etiology. Further genetic studies are needed.
 

Clinical outcomes and prognostic factors in triple-negative invasive lobular carcinoma of the breast.

Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. The median age at diagnosis for women with TN-ILC was 67years compared to 58years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001). Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Clinical Profile and Predictors of Survival in Carcinoma Penis Patients

Carcinoma penis is a rare neoplasm, and the literature is scarce on long-term survival and its predictors. The aim of the study was to determine the clinical profile and management patterns, identify predictors of survival, and the impact of education and rural/urban dwelling on survival. Patients with a histological diagnosis of carcinoma penis from January 2015 to December 2019 were included in the study. Demographics, clinical profile, education status, primary residence address, and outcomes were obtained from the case records. Distance from the treatment centre was obtained from the postal code. The primary objectives were to assess relapse-free survival (RFS) and overall survival (OS). The secondary objectives were to identify the predictors of RFS and OS and to determine the clinical profile and treatment patterns in patients with carcinoma penis in India. Time-to-event was calculated by Kaplan-Meir analysis and survival was compared by the log-rank test. Univariate and multivariable Cox regression analyses were used to find independent predictors of relapse and mortality. Logistic regression analyses to examine the associations of rural residence, education status, and distance from the treatment centre with the relapse adjusting for measured confounding variables. Case records of 102 patients treated during the above period were retrieved. The median age was 55.5 (interquartile range [IQR] 42-65 years). Ulcero-proliferative growth (65%), pain (57%), and dysuria (36%) were the most common presenting features. Clinical examination or imaging revealed inguinal lymphadenopathy in 70.6% of patients, however, only 42% of these lesions were pathologically involved. A total of 58.8% of patients were from rural areas, 46.9% had no formal education, and 50.9% had a primary residence ≥100 km from the hospital. Patients with lower education and rural households had higher TNM stages and nodal involvement. Median RFS and OS were 57.6 months (15.8 months to not reached) and 83.9 months (32.5 months to not reached), respectively. On univariate analysis tumor stage, involvement of lymph nodes, T stage, performance status, and albumin was predictive for relapse and survival. However, on multivariate analysis, the stage remained the only predictor of RFS and nodal involvement, and metastatic disease was a predictor of OS. Education status, rural habitation, and distance from the treatment centre were not predictors for relapse or survival. Patients with carcinoma have locally advanced disease at presentation. Rural dwellings and lower education were associated with the advanced stage but did not have a significant bearing on the survival outcomes. The stage at diagnosis and nodal involvement is the most important predictor of RFS and OS.

PD-L1 and HLA-class I expression status and their therapeutic implication in oesophageal small-cell carcinoma.

Oesophageal small-cell carcinoma is a rare and highly aggressive subtype of oesophageal cancer with a dismal prognosis. To explore the potential applicability of immunotherapy, we investigated the expression status of programmed death ligand 1 (PD-L1) and human leukocyte antigen (HLA)-class I and the degree of tumour-infiltrating lymphocytes (TILs) in oesophageal small-cell carcinoma. PD-L1 and HLA-class I expression levels were evaluated in 10 pure small-cell carcinomas and five mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). The combined positive score (CPS) and tumour proportion score (TPS) were used for PD-L1 assessment. Immunohistochemistry for mismatch repair (MMR) proteins was also performed. PD-L1 immunohistochemistry demonstrated CPS ≥1 in nine (60%), CPS ≥10 in five (33%), and TPS ≥1 in five (33%) cases. Overall survival was significantly longer in patients with CPS ≥1 than in those with CPS <1. HLA-class I deficiency (>50% tumour cells) was noted in five cases (33%), with no significant correlation with PD-L1 expression status. Among the five MiNENs, HLA-class I expression was decreased in the small-cell carcinoma component of three cases. HLA-class I deficiency was significantly associated with higher TNM stage and reduced TIL levels. MMR deficiency was not observed in any case. Given that a significant subset (40%) exhibited PD-L1 CPS ≥1 with preserved HLA-class I expression and high levels of TIL, the PD-1/PD-L1 pathway is a potential therapeutic target for oesophageal small-cell carcinoma.

Low Expression of TSTD2 Serves as a Biomarker for Poor Prognosis in Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) is a common cancer in people worldwide, and one of the main issues is developing suitable biomarkers. This study aims to investigate the expression of TSTD2 in KIRC and its impact on prognosis. RNA sequencing data from TCGA and GTEx were gathered to examine the functional enrichment of TSTD2-related differentially expressed genes (DEGs) using GO/KEGG, GSEA, immunocyte permeation analysis, and protein-protein interaction (PPI) network analysis. The Kaplan‒Meier-Cox regression model and the prognostic nomograph model were used to assess the clinical importance of TSTD2 in KIRC. R software was used to analyze the included studies. Finally, verification of cells and tissues was performed using immunohistochemical staining and quantitative real‒time PCR. In contrast to normal samples, it was discovered that TSTD2 was underexpressed in a number of malignancies, including KIRC. Furthermore, in 163 KIRC samples, low expression of TSTD2 was linked to a poor prognosis, as were subgroups with age greater than 60, the integrin pathway, the development of elastic fibers, and high TNM stage, pathologic stage, and histologic grade (P < 0.05). Age and TNM stage were included in the nomogram prognostic model, and low TSTD2 was a prognostic predictor that could be used independently in Cox regression analysis. In addition, 408 DEGs with 111 upregulated genes and 297 downregulated genes were found between the high- and low-expression groups. The diminished expression of TSTD2 may serve as a biomarker for unfavorable outcomes in KIRC, and holds potential as a target for therapeutic interventions.

The Prognostic Utilities of Various Risk Factors for Laryngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Objective: To assess the prognostic utilities of various risk factors for laryngeal squamous cell carcinoma. Methods: Six databases were searched to January 2022. Hazard ratios for overall survival and disease-free survival were collected and study characteristics were recorded. The risk of bias was evaluated using the Newcastle-Ottawa scale. Results: Twenty-eight studies involving 32,128 patients were finally included. In terms of overall survival, older age, a history of alcohol consumption, a high Charlson comorbidity index score, a high TNM stage (III and IV), a high tumor stage (III and IV), nodal involvement, poor pathological differentiation, primary chemoradiotherapy and radiotherapy were associated with increased risks of death. In terms of disease-free survival, older age (≥60 years), TNM stages III and IV, tumor stages III and IV, supraglottic tumors, and nodal involvement all increased the risk of death. Conclusions: The TNM stage importantly predicts overall survival, and tumor location predicts the disease-free survival of patients with laryngeal squamous cell carcinoma. Of patients with risk factors, the Charlson comorbidity index usefully predicts overall survival.

Anxiety and depression during 3-year follow-up period in postoperative gastrointestinal cancer patients: prevalence, vertical change, risk factors, and prognostic value.

Anxiety and depression are common issues in gastrointestinal cancer, bringing negative impacts on patients' quality of life and long-term prognosis. This study aimed to identify the prevalence, longitudinal variation, risk factors, and prognostic value of anxiety and depression in postoperative gastrointestinal cancer patients. A total of 320 gastrointestinal cancer patients after surgical resection (210 colorectal cancer (CRC) patients and 110 gastric cancer (GC) patients) were enrolled in this study. During the 3-year follow-up period, Hospital Anxiety and Depression Scale (HADS)-anxiety (HADS-A) and HADS-depression (HADS-D) scores were determined at baseline, 12th month (M12), 24th month (M24), and 36th month (M36). The prevalence of anxiety and depression at baseline was 39.7% and 33.4% in postoperative gastrointestinal cancer patients, respectively. Female (vs. male), single/divorced/widowed (vs. married), CRC (vs. GC), hypertension, higher TNM stage, neoadjuvant chemotherapy, and postoperative complications were independent risk factors of anxiety or depression in patients with gastrointestinal cancer (all P < 0.050). Furthermore, anxiety (P = 0.014) and depression (P < 0.001) were associated with shortened overall survival (OS); after further adjustment, depression was independently linked with shortened OS (P < 0.001), while anxiety was not. During the follow-up period, HADS-A score (from 7.78 ± 3.180 to 8.57 ± 2.854, P < 0.001), HADS-D score (from 7.23 ± 2.711 to 8.01 ± 2.786, P < 0.001), anxiety rate (from 39.7 to 49.2%, P = 0.019), and depression rate (from 33.4 to 42.6%, P = 0.023) were all gradually increased from baseline to M36. Anxiety and depression gradually exacerbate and relate to poor survival in postoperative gastrointestinal cancer patients.

TIGIT as a Novel Prognostic Marker for Immune Infiltration in Invasive Breast Cancer.

To assess the levels and potential therapeutic and prognostic significance of TIGIT in invasive breast cancer. The Cancer Genome Atlas database was used to evaluate TIGIT levels in invasive breast cancer and its association with clinicopathological features. Immunohistochemistry (IHC) was performed to validate it. Further, the Kaplan-Meier survival curve, univariate and multivariate Cox regression models were applied in analyzing the role of TIGIT in the prognosis of invasive breast cancer. Go / KEGG enrichment analyses techniques were used to investigate the possible cellular mechanism, and string database was used to explore TIGIT-related proteins. Finally, the TIMER database was used to determine the association between TIGIT and immune cell infiltrations. TIGIT was differentially expressed in Pan cancer tissues compared with normal tissues. Relative to normal tissues, TIGIT levels in invasive breast cancer were elevated (p<0.05). TIGIT mRNA level was significantly different from T stage, age, ER and PR level (p<0.05). The high levels of TIGIT exhibited positive correlations with PFI and OS (p<0.05). Univariate analysis revealed that age, clinical stage, high TNM stage, menopausal status and radiotherapy were the factors affecting OS (p< 0.05). Multivariate analysis revealed that age, high clinical stage and menopausal status were independent risk factors for tumor progression (p<0.05). CD226, INPP5D, PVR, PVRL2 and PVRL3 proteins interact with TIGIT. The TIGIT levels were significantly correlated with infiltrations of immune cells (such as CD8+ T cells) (r=0.917, p<0.05). TIGIT is elevated in invasive breast tumor and is closely associated with the prognosis of invasive breast cancer. TIGIT may be the target of immunotherapy for invasive breast cancer.

Epidemiological trends and novel prognostic evaluation approaches of patients with stage II-IV colorectal neuroendocrine neoplasms: A population-based study with external validation.

This study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification. Among all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital's independent cohort of 62 patients with CRNENs was used as the external validation cohort. In the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90-5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient. Over the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.

Clinical and Prognostic Impact of the Warburg Effect in Esophageal Carcinoma: Monocarboxylate Transporters as Candidates for Therapeutic Targeting

Introduction: Esophageal cancer (EC) seems to display increased glycolytic activity, but clinical studies on the expression/prognostic significance of glycometabolism-related proteins, as well as functional assays, are missing. Methods: Expression of 10 glycolytic biomarkers was evaluated by immunohistochemistry in tissue sections from 95 patients. Two esophageal squamous cell carcinoma (ESCC) cell lines were used to assess the effect of monocarboxylate transporter (MCT) downregulation on cell viability and extracellular lactate/glucose accumulation. Results: Expression of MCT1, MCT4, CD147, and GLUT1 was significantly associated with an ESCC histopathology, while a poor clinicopathological profile was seen in GLUT1- and LDHA-positive EC cases. In the ESCC group, MCT1 immunoreactivity is associated with high TNM stage and metastasis. The 3-year overall survival (OS) rate was significantly influenced by MCT4 and CAIX positivity and HKII negativity. Those biomarkers were considered independent prognostic factors of OS in multivariate analysis. Dual inhibition of MCT1/4 expression decreased cell viability and extracellular lactate accumulation in ESCC cells. Conclusion: Elevated glycolytic rates correlate with a poor clinicopathological profile in EC patients. MCT4 and CAIX positivity independently predict a worse prognosis. Due to the lack of information on treatment modalities, we could not further infer the role of these biomarkers in predicting response to therapy, which needs to be assessed in future studies. In addition, MCT1/4 targeting should be performed both “in vitro” and “in vivo” to further explore its impact on tumor growth and response to classical therapies. HKII expression and function, particularly in the tumor stroma, should be investigated.

Expression of Her-2/NEU in Patients With Primary Non-small Cell Lung Cancer (Nsclc)

Introduction: Now a days immunohistochemistry and genomic testing for patient with Non- Small Cell Lung Cancer (NSCLC) is becoming new standard of care in clinical decision making. A renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Aim of this present study was clinicopathological correlation of HER-2/neu expression by IHC in NSCLC. Method: This was a Cross sectional and observational study done at Sir Salimullah Medical College and National Institute of Disease of the Chest and Hospital (NIDCH) and other private hospitals in Dhaka city during July / 2014 to June / 2016. Adult of both gender with histologically diagnosed as a case of NSCLC was include in the study. Immunohistochemistry was done to see the positivity for HER/neu and clinical characteristics were observed. Result: A total 45 patients with NSCLC were enrolled in the study. Male was 77.8% (n=35) and female was 22.2% (n=10). The mean age was 55.67 (SD± 12) years and mean age of male was higher compared to female (57.54±11.64 years verses 49.1±11.38 years). Most of the male were smokers (71.1%) and female were nonsmokers (90%). 57.78% (n=26) of patients and 42.22% (n=19) of patients had adenocarcinoma and squamous cell carcinoma respectively. Most squamous cell carcinoma patients were elderly, had wasting and having higher TNM staging. Serum LDH level was higher with advance staging and grading. Only 8.89% (n=4) had HER-2/neu positive expression affected by male. Patients with HER 2/neu positive expression were relatively older (mean age 62.5±17.08). However, there were equal in histopathological categorization (50% SCC and 50% Adenocarcinoma). Mean LDH was slightly higher in HER-2 positive patients was compared to HER-2 negative patients (569.5±232.6 versus 469.7±181.8). Conclusion: About nine percent of patients having HER-2/neu positive was relatively older and had more high level of LDH. A large-scale study should be conducted in Bangladeshi population to characterize epidemiological, clinicopathological feature in patients with NSCLC with HER-2 expression. J Dhaka Med Coll. 2021; 29(1): 99-110

Up-regulated PIF1 predicts poor clinical outcomes and correlates with low immune infiltrates in clear cell renal cell carcinoma.

Background: Petite Integration Factor 1 (PIF1) is a multifunctional helicase and DNA processing enzyme that plays an important role in the process of several cancer types. However, the relationship between clear cell renal cell carcinoma (ccRCC) and PIF1 remains unclear. This study aims to explore the role of PIF1 in ccRCC tumorigenesis and prognosis. Methods: Based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, we retrieved and verified the expression of PIF1 in ccRCC tissues as well as normal tissues. To assess the protein expression of PIF1 by using the Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). We also performed receiver operating characteristic (ROC) curve analysis to differentiate the effectiveness of PIF1 in ccRCC and adjacent normal tissues. To evaluate the value of PIF1 on clinical outcomes in ccRCC patients by using multivariate methods and Kaplan‒Meier survival curves. Protein‒protein interaction (PPI) networks were made with STRING. We determined the relationship between the expression of PIF1 and immune cell infiltration with single-sample gene set enrichment analysis (ssGSEA). Results: Compared with normal tissues, the expression of PIF1 was significantly elevated in ccRCC. The mRNA expression of PIF1 is correlated with high TNM stage and high pathologic stage. The receiver operating characteristic (ROC) curve analysis showed that PIF1 was related to an area under the curve (AUC) value of 0.928 to distinguish between ccRCC tissues and normal tissues. Kaplan‒Meier survival analysis showed that the overall survival (OS) of ccRCC patients with a high level of PIF1 was significantly shorter than that of those with a low level of PIF1. PIF1 may play an important role in the occurrence of tumors. Correlation analysis showed that PIF1-mediated carcinogenesis may participate in the process of tumor immune escape in ccRCC. Conclusion: PIF1 could be a reference biomarker to identify ccRCC patients with poor prognosis. PIF1 may play a distinct role in the microenvironment of ccRCC by regulating tumor infiltration of immune cells, which is a new therapeutic target to affect the growth of the tumor.

Primary adenocarcinoma of colon: A clinicopathological study with the prevalence and correlation of CDX2 biomarker expression - A tertiary care center experience.

Colorectal cancer is one of the alarming health problems worldwide. Prognostic biomarkers are the key for risk stratification in patients with colon cancer and the decision to recommend adjuvant chemotherapy. It has been difficult to identify a single prognostic biomarker for colon cancer. Currently, tumor stage, tumor grade, and microsatellite instability remain the most important prognostic variables that aid in the treatment of patients with colon cancer. Some studies highlighted that CDX2 immunohistochemistry negativity is an independent prognostic factor and indicates a worse survival rate. Our aim was to study the prevalence of CDX2 biomarker expression in patients diagnosed with primary adenocarcinoma and to correlate this with the clinical profile and pathological features. Endoscopic mucosal biopsies and resection specimens of 148 patients diagnosed with colonic adenocarcinoma were analyzed. CDX2 immunohistochemistry was performed, and the result was correlated with clinicopathological features. The results were presented as mean, frequencies, and percentages. Pearson's Chi-square test was used to assess the associations between clinicopathological parameters and CDX2 immunohistochemistry negativity. The prevalence of CDX2 expression by immunohistochemistry in colon cancer was found to be 92%. CDX2 biomarker negativity was found to be higher in left-sided colon cancers, poorly differentiated adenocarcinoma, mucinous carcinoma, and higher TNM stages. CDX2-negative tumors are often associated with several adverse prognostic variables (e.g., advanced stage, poor differentiation, and metastasis). Thus, sub-classification of colon cancer based on the CDX2 biomarker aids to separate them into prognostically relevant categories.

Comparison of GLIM and PG-SGA for predicting clinical outcomes of patients with esophageal squamous carcinoma resection.

to determine the validity of the Global Leadership Initiative on Malnutrition (GLIM) against the Patient Generated-Subjective Global Assessment (PG-SGA) as a gold standard tool in malnutrition diagnosis, and to assess the impact of malnutrition diagnosed using GLIM and PG-SGA on the clinical outcomes of patients with esophageal squamous carcinoma (ESCC) resection. we prospectively analyzed 182 patients with ESCC who underwent radical esophagectomy. Preoperative malnutrition was diagnosed using GLIM and PG-SGA, and the postoperative clinical outcomes, including postoperative complications, postoperative chest tube indwelling time, length of stay and total hospitalization cost, were recorded. The association between the prevalence of malnutrition defined by the two tools and postoperative clinical outcomes was evaluated. among the 182 ESCC patients, the incidence of malnutrition before surgery was 58.2 % and 48.4 % defined by PG-SGA and GLIM, respectively. GLIM and PG-SGA had good consistency in nutritional assessment of ESCC patients (k = 0.628, p < 0.001). Malnourished patients had higher TNM stages and older ages (all p < 0.05). Patients with malnutrition as assessed by PG-SGA and GLIM had a higher incidence of postoperative complications, a longer indwelling time of chest tube after esophagectomy, longer hospital length of stay, and higher hospitalization costs than patients with good nutrition (p < 0.001). Comparing the predictive efficiency of postoperative complications, the sensitivity of PG-SGA- and GLIM-defined malnutrition were 81.6 % and 79.6 %, the specificity were 50.4 % and 63.2 %, the Youden index were 0.320 and 0.428, and the Kappa value were 0.110 and 0.130, respectively. The areas under ROC curve of PG-SGA- and GLIM-defined malnutrition and postoperative complications were 0.660 and 0.714, respectively. this study indicates the effectiveness of malnutrition diagnosed according to GLIM and PG-SGA in predicting postoperative clinical outcomes among patients with ESCC. Compared with PG-SGA, GLIM criteria can better predict postoperative complications of ESCC. Follow-up analysis of postoperative long-term survival is needed to explore the association between different assessment tools and postoperative long-term clinical outcomes.

MEME KANSERİNDE NÖTROFİL-LENFOSİT ORANI VE PLATELET-LENFOSİT ORANININ KLİNİKOPATOLOJİK ÖNEMİNİN ARAŞTIRILMASI

AIM: In this study, we aimed to examine whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values of women operated for breast cancer were associated with their clinicopathological features.&#x0D; MATERIAL AND METHOD: The data of 463 females who were operated for breast cancer in our center between Januray 2015 and December 2020 were analyzed retrospectively. Age, menopausal status, hematological values, histopathological features of tumors, presence of hormone receptors, surgical and biopsy techniques were evaluated in detail. NLR and PLR values were calculated using the results of routinely performed hemogram test before the operation, and their relationships with all parameters were analyzed. &#x0D; RESULTS: The ages of the cases ranged from 23 to 88 years, with a mean of 53.57 ± 12.66. Postmenopausal women constituted 62.42% of the cases. A negative correlation was found between age and PLR, but neither PLR nor NLR were found to be associated with menopause status. It was found that high NLR value was associated with high N stage, high TNM stage, high number of metastatic lymph nodes and presence of extracapsular invasion (p

Extracellular Vesicle Membrane Protein Profiling and Targeted Mass Spectrometry Unveil CD59 and Tetraspanin 9 as Novel Plasma Biomarkers for Detection of Colorectal Cancer.

Extracellular vesicles (EVs) are valuable sources for the discovery of useful cancer biomarkers. This study explores the potential usefulness of tumor cell-derived EV membrane proteins as plasma biomarkers for early detection of colorectal cancer (CRC). EVs were isolated from the culture supernatants of four CRC cell lines by ultracentrifugation, and their protein profiles were analyzed by LC-MS/MS. Bioinformatics analysis of identified proteins revealed 518 EV membrane proteins in common among at least three CRC cell lines. We next used accurate inclusion mass screening (AIMS) in parallel with iTRAQ-based quantitative proteomic analysis to highlight candidate proteins and validated their presence in pooled plasma-generated EVs from 30 healthy controls and 30 CRC patients. From these, we chose 14 potential EV-derived targets for further quantification by targeted MS assay in a separate individual cohort comprising of 73 CRC and 80 healthy subjects. Quantitative analyses revealed significant increases in ADAM10, CD59 and TSPAN9 levels (2.19- to 5.26-fold, p < 0.0001) in plasma EVs from CRC patients, with AUC values of 0.83, 0.95 and 0.87, respectively. Higher EV CD59 levels were significantly correlated with distant metastasis (p = 0.0475), and higher EV TSPAN9 levels were significantly associated with lymph node metastasis (p = 0.0011), distant metastasis at diagnosis (p = 0.0104) and higher TNM stage (p = 0.0065). A two-marker panel consisting of CD59 and TSPAN9 outperformed the conventional marker CEA in discriminating CRC and stage I/II CRC patients from healthy controls, with AUC values of 0.98 and 0.99, respectively. Our results identify EV membrane proteins in common among CRC cell lines and altered plasma EV protein profiles in CRC patients and suggest plasma EV CD59 and TSPAN9 as a novel biomarker panel for detecting early-stage CRC.

LINC00324 in cancer: Regulatory and therapeutic implications.

LINC00324 is a 2082 bp intergenic noncoding RNA. Aberrant expression of LINC00324 was associated with the risk of 11 tumors and was closely associated with clinicopathological features and prognostic levels of 7 tumors. LINC00324 can sponge multiple miRNAs to form complex ceRNA networks, and can also recruit transcription factors and bind RNA-binding protein HuR, thereby regulating the expression of a number of downstream protein-coding genes. LINC00324 is involved in 4 signaling pathways, including the PI3K/AKT signaling pathway, cell cycle regulatory pathway, Notch signaling pathway, and Jak/STAT3 signaling pathway. High expression of LINC00324 was associated with larger tumors, a higher degree of metastasis, a higher TNM stage and clinical stage, and shorter OS. Currently, four downstream genes in the LINC00324 network have targeted drugs. In this review, we summarize the molecular mechanisms and clinical value of LINC00324 in tumors and discuss future directions and challenges for LINC00324 research.

AIF-1, a potential biomarker of aggressive tumor behavior in patients with non-small cell lung cancer.

Allogeneic inflammatory factor-1 (AIF-1) overexpression has been reported to be associated with tumorigenesis and tumor metastasis. This study aimed to investigate the role of AIF-1 in the development and progression of non-small cell lung cancer (NSCLC). AIF-1, IL-6, and VEGF expressions in human NSCLC tissue were examined by immunofluorescence staining. Bioinformatics analyses were performed to identify AIF-1-related molecules and pathways in NSCLC. Human lung cancer A549 cell proliferation was assessed by CCK-8 assay, and cell migration was evaluated with wound-healing assay. IL-6 and VEGF secretions in A549 cell culture supernatants were quantified using the Elecsys IL-6 immunoassay kit and Vascular Endothelial Growth Factor Assay Kit. RT-PCR and western blot were performed to quantify the expressions of AIF-1, IL-6, and VEGF mRNAs and proteins involved in p38-MAPK and JAK/STAT3 signaling such as p-p38 and p-STAT3. The effects of AIF-1 on A549 cell proliferation and the expressions of IL-6 and VEGF were assessed using SB203580 and ruxolitinib. The results showed that AIF-1 expression was higher in human NSCLC tissue than that in paracancer tissue. High AIF-1 expression was associated with metastasis, higher TNM stage, and poorer survival. Bioinformatics connected AIF-1 to JAK/STAT signaling in NSCLC. AIF-1 increased A549 cell proliferation, migration, IL-6 secretion and, VEGF secretion, and these effects were attenuated by inhibition of p38-MAPK or JAK/STAT3 signaling. In conclusion, AIF-1 may promote aggressive NSCLC behavior via activation of p38-MAPK and JAK/STAT signaling.

Comprehensive analysis of cuproptosis-related genes in prognosis, tumor microenvironment infiltration, and immunotherapy response in gastric cancer.

Cuproptosis is the most recently identified copper-dependent cell death form that influences tricarboxylic acid (TCA) cycle. However, the relationship between cuproptosis and clinical prognosis, tumor microenvironment infiltration (TME), and response to immunotherapy remains unclear. Single-sample gene-set enrichment analysis (ssGSEA) was employed to construct cuproptosisScore (cpS) and 1378 gastric cancer (GC) patients from five independent public datasets were classified into high- or low-cpS groups according to the median of cpS. Then the impacts of cuproptosis on tumor microenvironment infiltration (TME), biological function, response to immunotherapy, and clinical prognosis of GC were evaluated. RiskScore and nomogram were constructed using Lasso Cox regression algorithm to validate its predictive capability in GC patients. Compared to patients with high cpS, patients with low cpS exhibited poorer prognosis, higher TNM stage, and stronger stromal activation. Meanwhile, the analysis of response to immunotherapy confirmed patients with high cpS could better benefit from immunotherapy and had a better susceptibility to chemotherapeutic drugs. Then, 9 prognosis-related signatures were collected based on differentially expressed genes (DEGs) of cpS groups. Finally, a riskScore model was constructed using the multivariate Cox (multi-Cox) regression coefficients of prognosis-related signatures and had an excellent capability of predicting 1-, 3-, and 5-year survival in GC patients. This study revealed the role of curproptosis in TME, response to immunotherapy, and clinical prognosis in GC, which highlighted the significant clinical implications of curproptosis and provided novel ideas for the therapeutic application of cuproptosis in GC.